Patent GB-921536-A (GB)
Title: Substituted n-hydroxyureas and a process for their manufacture
Inventor: STEINBRUNN GUSTAV
Filed: 1961-02-16
Abstract: The invention comprises compounds (excepting N-phenyl-N1-hydroxyurea) of the general formulae <FORM:0921536/IV(a)/1> and <FORM:0921536/IV(a)/2 may be mono-, di- or tri-substituted by alkyl containing 1 to 4 carbon atoms, alkenyl containing 2 to 3 carbon atoms, alkoxy contain1 to 2 carbon atoms, chlorine or bromine; alkyl containing 1 to 8 carbon atoms; aralkyl containing 1 carbon atom in the alkyl component; halogenalkyl in which the halogen is chlorine or bromine and which contains 1 to 4 carbon atoms; halogenaralkyl in which the halogen is chlorine or bromine and which contains 1 or 2 carbon atoms in the alkyl component; cyanoalkyl containing 1 to 4 carbon atoms; cyanoaralkyl containing 1 to 2 carbon atoms in the alkyl component; cycloalkyl containing 6 to 8 carbon atoms as ring members; alkenyl containing 2 to 3 carbon atoms; alkinyl containing 3 to 5 carbon atoms; halogenalkinyl containing 3 to 5 carbon atoms or a radical of the formula <FORM:0921536/IV(a)/3> wherein X represents hydrogen, methyl, chloromethyl, bromine or methoxyl and n is 1 or 2; R1 stands for phenylene or naphthylene which may be mono-, di- or tri-substituted by alkyl containing 1 to 4 carbon atoms, alkenyl containing 2 to 3 carbon atoms, chlorine or bromine; alkylene containing 2 to 8 carbon atoms; aralkylene containing 1 to 2 carbon atoms in the alkylene component; radicals of the formulae <FORM:0921536/IV(a)/4> or <FORM:0921536/IV(a)/5> or cycloalkylene containing 6 to 8 carbon atoms as ring members; R11 stands for hydrogen; alkyl containing 1 to 8 carbon atoms; hydroxyalkyl containing 1 to 8 carbon atoms; or alkenyl containing 3 carbon atoms. The invention also comprises a process for preparing the said compounds (including N-phenyl-N1-hydroxyurea) wherein 1 mol of an isocyanate of formula R-R=C=O or of a carbamyl chloride of formula <FORM:0921536/IV(a)/6> or 1/2 mol of a diisocyanate of formula O=C=N-R1-N=C=O or of a dicarbamyl chloride of formula <FORM:0921536/IV(a)/7> is added to 1 to 3 mols of a hydroxylamine of formula R11-NHOH at a temperature between 0 DEG  to 70 DEG C. in the presence of water and of an organic solvent which reacts neither with the isocyanate, diisocyanate, carbamyl chloride or dicarbamyl chloride nor with the hydroxylamine and, if a carbamyl chloride or a dicarbamyl chloride is used as starting material, in the presence of an acid-binding substance, R, R1 and R11 having the same meanings as stated above.  The reaction is advantageously carried out in the presence of a substance which is capable of forming complex compounds with metals, e.g. ethylenediaminotetraacetic acid or one of its salts.  Suitable solvents for the process include diethyl ether, b ,b 1-dichlorodiethyl ether, toluene, methylene chloride, chlorobenzenes, acetonitrile, dioxan, tetrahydrofuran and dimethyl sulphoxide as typical examples of those specified. Mixtures of these solvents may also be used.  The hydroxylamine is reacted in free form and is preferably liberated from one of its salts, e.g. the chloride, sulphite or acetate, by means of aqueous, alkaline solution. Examples illustrate the preparation of inter alia N-p-ethoxyphenyl-N1-hydroxyurea, N-p-tolyl-N1-hydroxyurea, N-m-chlorophenyl-N1-hydroxyurea, N - (2 - ethylhexyl)-N1-hydroxyurea, N-(g -chloropropyl)-N1-hydroxyurea, N-cyclooctyl - N1 - hydroxyurea, N - vinyl - N1 - hydroxyurea, N-phenyl-N1-ethyl-N1-hydroxyurea, N,N1-bis(hydroxycarbamyl)-naphthylene-1,5-diamine, N,N1-bis(N11-methyl-N11-hydroxy-carbamyl) - toluylene - 2,4 - diamine and N-p-toluenesulphonyl - N1 - hydroxyurea.  The N-hydroxyureas can be alkylated by conventional means; for example, N-m-tolyl-N1-methyl-N1-methoxyurea is obtained by treating N-m-tolyl-N1-hydroxyurea with dimethyl sulphate. The N-hydroxyureas can be used as intermediates for the production of pharmaceuticals or plant protection agents.